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Hjärtarytmiersjukdomshistoria och behandling
Nils Edvardsson
Normal sinusknutefunktion
* intrinsic rate
** 90-120 slag/min (ex. denervering vid
hjärttransplantation
** sjunker med åldern
** kronotropi – frekvensökning
* autonom styrning
** vagus dominerar (avtar med åldern)
*** vid max atropin HR 110-120
** sympaticus
*** vid max arbete HR 220 - åldern
Sjuk sinusknuta – diagnostik
* Förmaksbradyarytmi (paroxysmal eller generell)
** sinusbradycardi (<40 slag/min)
** sinus arrest (> 3 s)
** sino-atrialt block
** kronotrop insufficiens
* Paroxysmala tachyarytmier
** oftast förmaksflimmer
Sjuk sinusknuta – incidens, prevalens
* svårbestämd - unga friska kan ha bradycardier,
idrottsmän har ofta HR<40.
* incidens ca 0.2%
* ökar med åldern
Symptom
* specifika - syncope, yrsel, hjärtsvikt
* ospecifika - trötthet, orkselöshet, apati, depression
* hjärtklappning
** paroxysmala FF, FFl, andra tachycardier
** inappropriate sinus node tachycardia, IST
** trombembolism!
”Sinus node remodelling”
* En inaktiv sinusknuta ”somnar in”
** fungerar inte normalt efter en tid
** kan ses övergående efter elkonvertering
(riskperiod för proarytmi)
** avtagande sinusfrekvens - nodalrytm
* Kronotrop insufficiens
** välbekant men ej lättdefinierat begrepp
** ”otillräcklig frekvensvariation i samband
med fysisk ansträngning”
AV-block
* AV-block I (PR>0.22 s)
* AV-block II:I (Wenchebach)
** oftast beläget I AV-noden (intra-nodalt)
* AV-block II:II
** oftast beläget nedanför AV-noden (infranodalt)
** pacemakerindikation
* AV-block III (oberoende förmaks- och
kammarrytm)
Vänstergrenblock - LBBB
* alltid ett observandum
- markör!
* någon gång rest efter myokardit – i princip ofarligt
om myokardiet friskt
* vanligt vid allvarliga tillstånd som klaffel
(aortastenos), VK-kardiomyopati,
kranskärlssjukdom, VK-svikt, etc.
LBBB
V1
V6
V1
LBBB – normal electrical axis
V2
V3
V4
V5
V6
LAH-block = extremt vänsterställd
el-axel
* QRS-komplexet ofta <120 ms
* Vanligt hos äldre, avspeglar (lindrig) hjärtsjukdom
hos ca 50%
Enkel diagnostik:
** om R/S-kvoten är 0 eller negativ i II
** och mer negativ i III
** föreligger extremt vänsterställd el-axel (minst -30º)
RBBB
Högergrenblock - RBBB
* vanligt med partiella RBBB, anomali,
”högersidigt intraventrikulärt ledningshinder”
* hos yngre - tänk på ASD
* hos äldre vanligare - ingen ökad risk
Ovanligt men viktigt: högerkammarsjukdom,
t.ex. ARVD (arytmogen högerkammardysplasi)
Uttalat vänstersidigt
intraventrikulärt ledningshinder
* QRS >120 ms, oftast betydligt mer
* uppfyller inte strikta kriterier för LBBB
* betyder att konduktionen är drabbad mer
perifert på grund av utbredd myokardskada
Bifascikulärt block – BBBB
* oftast RBBB+LAH, mycket sällan RBBB+LPH:
* BBBB utan symptom: expektans
* BBBB med yrsel/syncope: risk för AVblock III cirka 6% per år
* BBBB+AV-block I: risk för AV-block III
cirka 30% per år – pacemaker!
Primary VF
Monomorphic VT
Moe
Mirowski
Appropriate shocks
Behandling av VT/VF
* Farmakologisk behandling kan vara riskabel,
risk för proarytmi
* Implanterbar defibrillator
** overdrive pacing vid VT
** shock vid snabb VT och VF
* Shockreduktion (betablockad, amiodarone,
sotalol)
V1
V2
V3
V4
V5
V6
921003
22 y, professional
ice-hockey goalkeeper
WPW-syndrome
In total 5 procedures at
three centres in the US
before cured
921006
♂ 19 y, soccer goalkeeper
Palpitations during match, cured by RF
ablation
WPW syndrome
Preexcitation in 0.1-0.3 ‰ in general population
Tachyarrhythmias in about half of them
High risk patients rare - multiple pathways
- antidromic tachycardia
- preexcited AF
Sudden cardiac death very rare
RF ablation is an effective cure
WPW syndrome
Left lateral pathway – RF ablation
♂23y, professional tennis player.
AVNRT
Paroxysmal
tachycardias,
before, but
not enough to
motivate
treatment
Had to give up
an important
match in 5th set
when in winning
position.
Tachycardia
started
during game and
stopped only after
end of ”injury
time”
Cured by
RF ablation
AV nodal reentry tachycardia
AVNRT
3 %o in general
population
Women:men 6:1
Fast
pathway
Palpitations,
syncope,
urina spastica
Sudden onset,
sudden offset
Slow pathway
Adenosin stops tachycardia by short block in AV node
Heart rate during
tachycardia (140)
180-240 bpm
AVNRT - Slow pathway ablation
HBE
SC
RF
RV
Efficacy
>95%
Patient
cured
for life
14 mån efter
RF-ablation av
AVNRT
Startkänslan
Maj 2004
AVNRT
♂ 23 y, soccer defender in elite division
PP 380 ms
EAT
Ectopic atrial tachycardia, EAT
* focal or reentry
* intermittent or persistent
* may cause LV dysfunction
* can be life-threatening
in children and young
patients
Start of atrial fibrillation
P on T
PAC
PAC – atrial fibrillation
Requisits for atrial fibrillation
Regulator
AV node
Autonomic tone
Trigger
 Premature atrial beats
 Bursts from pulmonary veins
 Bradycardia
Terminator
AF
Initiator
Perpetuator
 Spatial dispersion of








refractory periods
Short wave length
Functional blocks
Large atria
Diseased areas
Anatomical blocks
Short wave length
Short excitable gap
Triggers
Autonomic trigger patterns
Euro Heart Survey, 1517 pts with paroxysmal AF
De Vos et al., Eur Heart J 2008
Acute, paroxysmal AF
Self-terminating <7d, mostly <48h
Symptoms: palpitations, anxiety,
dizziness etc
Risk: depending on additional factors
Treatment goal: symptom relief, eliminate or reduce attacks, reduce heart rate
during attacks
Strategy: rhythm control (and rate control), consider anticoagulation
Persistent: duration >7d, will not stop spontaneously but can be
converted. Long-standing persistent, duration > 1 year
May be asymptomatic, little or very symptomatic: at rest?, on exertion?
Risk: depending on additional risk factors
Treatment goal: relief of symptoms, reduce risk
Treatment: rhythm control (+ rate control) + antithrombotic treatment
Permanent or ”accepted”:
will not stop spontaneously and/or
cannot be converted
May be asymptomatic, little or very symptomatic: at rest?, on exertion?
Risk: depending on comorbidity
Treatment goal: relief of symptoms, reduce risk
Treatment: rate control + antithrombotic treatment
Atrial fibrillation
Variable conduction via the AV node to
the ventricles
II
Right atrium
Left atrium
Atrial rate 350-500 bpm
Patient 1
51 years old, male, accountant with own company, two elder
brothers with AF, while he himself is sofar healthy.
PAF diagnosed one year ago after golf and whisky, propranolol
(Inderal). Increasing number of episodes, almost always after
tennis, skiing, golf, often starting during the night afterwards.
Sotalol (Sotacor), better. Worse again, tested dispopyramide
(Dirytmin), verapamil (Isoptin).
More frequent episodes, longer duration, more easily starting,
need for DC. Amiodarone (Coradrone). AF interfering with work.
Patient 1
Finally very limited in his life, can not sport, can not
participate in social life, no wine/whisky.
Persistent AF alternating with self-terminating
episodes.
Ready for non-pharmacological treatment.
Duration from first attack to heavily symptomatic,
therapy resistant AF was 8 years.
Page 1 and 7/10
Atrial flutter:
more organized, one circuit, atrial rate 280 bpm, various
degrees of blocked conduction to the ventricles, here 3:1
Occurs as an entity of its own but very often together with atrial
fibrillation. Treated mainly in the same way but often difficult to
treat pharmacologically. Ablation!
ACC/AHA/ESC Guidelines for Management of Atrial Fibrillation
Progression of AF
Paroxysmal
Persistent
Permanent
Sinus Rhythm
DC
Atrial Fibrillation
AF is associated with increased
morbidity and mortality
Adjusted relative risk
3.5
Mortality
3.0
2.5
2.0
1.5
1.0
0.5
0
Morbidity
Stroke
NonNonCV
Total
mortality stroke
CV mortality mortality
mortality mortality
Stroke
CHF
MI
Manitoba Heart Study; Am J Med 1995
AF- a problem growing with age
U.S. population
x 1000
Population with AF
x 1000
Population with
atrial fibrillation
30,000
500
400
20,000
300
U.S. population
200
10,000
100
0
<5 5- 10- 15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65- 70- 75- 80- 85- 90- >95
9 14 19 24 29 34 39 44 49 54 59 64 69 74 79 84 89 94
0
Age, yr
Adapted from Feinberg WM. Arch Intern Med 1995;155:469-473
Atrial fibrillation – the future
Adults with atrial fibrillation, in millions
7.0
6.0
5.0
4.78
5.16
5.42
5.61
4.34
4.0
3.80
3.33
3.0
2.0
2.94
2.08
2.26
2.44
2.66
1.0
0
1990
2000
2010
2020
2030
2040
2050
Go et al., JAMA 2001
AF limits patients´ lifes
“I‘d love to go skiing again. It
makes me quite sad” (UK,
parox)
“I used to do all the housework
but now…I feel unable…to look
after my home” (Fr, Parox)
“I like going out, going to parties…
enjoying life…now I can’t” (Fr, perm)
“When it was bad we couldn’t
have sex” (Ge, pers)
“Even just considering
walking, it’s noticeable” (Fr,
Parox)
“Always worried …always
scared about tomorrow” (F,
parox)
“No more sport, nothing…physically
diminished. Heavy work, cycling, sport;
all out of the question ” (Fr, Parox)
“To cook, to have twelve people for
dinner, I can’t do those things” (US, Perm)
“In the short-term, I have trouble
going up and down the stairs” (US,
Parox)
“Everything is an effort, I
have no bounce” (Fr, Parox)
ACC/AHA/ESC Guidelines for Management of Atrial Fibrillation
Loss of atrial
function
Atrial
pressure
Atrial
thrombus
Embolism
Congestion
Dyspnea
Cardiac
output
Fatigue
Ventricular
filling
Stroke
volume
Rapid, irregular
ventricular rate
Cerebral
blood flow
Vertigo
Coronary
blood flow
Angina
pectoris
Myocardial
O2 demand
Palpitations
Cardiomyopathy
Impact on symptoms
Percentage of Atrial Fibrillation patients
experiencing these symptoms
Shortness
of breath
60%
Palpitations
53%
Fatigue
41%
Chest pain
25%
Dizziness
23%
Syncope
3%
0
10
20
30
40
50
NB!
Asymptomatic
episodes are
more frequent
than symptomatic,
are short in
duration and carry
the same risk for
stroke
60
Zimetbaum P et al., PACE 1999;22:782
ACC/AHA/ESC Guidelines for Management of Atrial Fibrillation
Management of AF - Rationale
Symptomatic relief
Palpitations
Dyspnea
Fatigue
Angina pectoris
Prevention of late complications
Embolic events
Cardiomyopathy
Prevention of progression of AF
Atrial fibrillation - strategies
Läkemedel och icke-farmakologisk behandling
* farmakologisk behandling
** rytmkontroll
** frekvenskontroll
** antikoagulation
* elkonvertering
* icke-farmakologisk behandling
** His-ablation
** pacing
** kateterablation
** kirurgi
** intra-operativ ablation
DC cardioversion, external,
biphasic shocks,
>80% success rate.
General anaesthesia
AF – pharmacological conversion
Comments
Class IC
- flecainide
- propafenone
effective, little/no heart disease, short AF
duration
effective, little/no heart disease, short AF
duration
Class III
- amiodarone
- sotalol
- ibutilide
variable efficacy
low efficacy, best post op.
effective, also post op., proarrhythmia
Vernakalant
effective when AF duration <1 week
Digoxin
no proven efficacy
AF6 - before and 2 w after DC
Responders – SR at follow-up
Q.
Baseline 12±3 d
1
2
3
4
5
6
1,2
5,0
4,4
3,4
5,3
2,7
Andningsbesvär i vila
Andningsbesvär vid ansträngning
Begränsningar i det dagliga livet
Obehagskänsla pga FF
Trötthet pga FF
Oro/ångest pga FF
1,0
3,2
2,1
1,5
2,5
1,8
Non-responders – did not have SR at follow-up
Q.
Baseline 12±3 d
1 Andningsbesvär i vila
2 Andningsbesvär vid ansträngning
3 Begränsningar i det dagliga livet
4 Obehagskänsla pga FF
5 Trötthet pga FF
6 Oro/ångest pga FF
0,8
3,9
2,3
1,8
3,7
1,5
0,9
3,6
2,9
1,9
3,1
1,6
Early relapse after DC cardioversion
RAFT – propafenone SR vs. placebo
* history of sympt. AF
* ECG proof < 12 mo
* SR at first dose of
randomized
medication
* outpatient initiation
* loading period d 1-4
* time to outcome
event
** from day 1
** from day 5
523 pts, mean age 63 years, >50% without structural heart disease. No
deaths, no VT.
Side effects leading to discontinuation: 13%, 13%, 14% and 25%
Dizziness, dyspnoea, taste disturbance, fatigue, constipation
Pritchett et al., Am J Cardiol 2003
Patients converted to SR within 3 months of
onset are more likely to remain in SR
Patients in sinus rhythm (%)
90
80
<3-month duration of atrial fibrillation prior to cardioversion
82%
>12-month duration of atrial fibrillation prior to cardioversion
67%
70
60
50
36%
40
27%
30
20
10
0
1 month
6 months
P<.02
P<.07
The longer one waits to initiate a rhythm-control strategy,
the harder it is to regain sinus rhythm
Dittrich HC et al. Am J Cardiol. 1989;63:193-197.
Tid från insatt Waran till DC
545 patienter, första elkonverteringen
B-M Abrahamsson, Sahlgrenska University Hospital
Recommended and
non-recommended
treatment in a ”realworld” setting
2007
AF – maintenance of sinus rhythm
Comments
Class IA
- disopyramide effective, limiting side effects
Class IC
- flecainide
- propafenone
Class III
- amiodarone
- dronedarone
- sotalol
- dofetilide
effective, little/no heart disease
effective, little/no heart disease
effective, complex and dangerous side
effects
moderately effective, low risk
effective, risk of proarrhythmia
effective, risk of proarrhythmia
Choice depending on underlying heart disease and risk of proarrhythmia.
Various endpoints in studies (time to relapse; no in SR at 1 y etc.)
Bazett´s formula 1918-20
QTc =
QT (s)
RR (s)
Rate correction to heart rate 60 bpm.
Over- and undercorrection at low-high heart rates.
Measure at a mean heart rate of 60-80-(100) bpm!!
Torsade de pointes
Starts with late PVC, QRS complex twisting around axis,
QT prolongation
AF a progressive disease, treat early
Paroxysmal
n
Age, y
Time from first AF, mo
Duration current AF, mo
CAD, %
Hypertension, %
Valvular, %
None, %
Heart failure, %
167
66
39
NA
12
17
10
46
14
Chronic
389
70
66
54
18
22
20
23
43
ALFA study – subsets of atrial fibrillation in general practice in France
Lévy et al, Circulation, 1999
Quality of warfarin treatment
Interational Normalized Ratio
Time in range (%)
100%
>3.2
80%
60%
66%
81%
2.0-3.0
40%
20%
<1.8
0%
3
6
9
12
15
18
Treatment duration (months)
21
CHADS2 score in patients with AF
C
H
A
D
S
congestive heart disease
hypertension
age <75 y
diabetes
TIA or stroke
C, H, A, D ger en poäng vardera, S ger två poäng
Andra risk scores under utvärdering, t.ex.
CHA2DS2Vasc och HAS-BLED.
Distribution of CHADS2 scores between 17097
women and 14724 men with stroke and AF
%
40
women
men
30
20
10
0
0
1
2
3
CHADS2 score
4
5
6
Pill in the pocket approach
In-hospital evaluation
268 pts in the ER, , 59±11 y, recent onset AF
propafenone 600 (450) mg OR flecainide 300 (200) mg orally
Rhythm monitoring 8 h, BP every 30 min, ECG every h
58 patients excluded (treatment failure, side effects)
Out-of-hospital treatment
210 pts, 165 (79%) had 618 recurrences
569 recurrences were treated 36±93 min after onset of symptoms.
Success criterion: conversion <6h, no side effects.
534 episodes (94%) interrupted <6h
* 16 episodes interrupted >6h, no emergency room contact
* 26 episodes involved emergency room contact
Time to resolution 113±84 min
Alboni et al., NEJM 351:2384-2391; 2004
Upstream therapy: ACE-I and ARB
Healey et al., JACC 2005
Upstream therapy: statins
Fauchier et al., JACC 2008
Dronedarone - ATHENA
* PAF or persistent AF
* >=75 y, or <75 y + 1 risk factor
* N=4628, mean age 72+-9 y, 47% females
* Follow-up 21+-5 months
* 25% in AF/Afl at randomization
* Approx. 1/3 CAD, 1/5 history of CHF NYHA II-III,
4% had EF<35%
* CV background medication – 71% betablockers,
70% ACE-I/ARB, 39% statins, 60% OAC
Dronedarone - ATHENA
Hohnloser et al., NEJM 2009
AV junctional ablation
Before
After
Invasive procedure
Destruction of the His bundle, intentional complete AV block
Palliation, symptomatic treatment - does not cure
Last resort in refractory patients
Permanent pacemaker needed, implanted prior to ablation
Maze surgery
Sleeves of LA – PV connections
Pulmonary
veins
Pulmonary vein isolation
Segmental
Lasso
RF
Immediately
 ≈90% successful
Long-term results
 60-80% freedom from
symptomatic
arrhythmia
with or without AA
 Techniques in
development!
Many remaining issues:
• Different techniques
• Triggers vs substrate
• Additional lines
• Selection of patients
• etc., etc.
Circumferential
Intraoperativ AF ablation
M 54, persistent AF 10 months
June 6, 2002 CABG + cryo
Survival among patients admitted for stroke and with
medical history of atrial fibrillation by CHADS2 score
1.00
Survival distribution function .
0.80
0.60
0.40
CHADS2 score
0.20
0
1
2
3
4
5
6
Months
0.00
0
6
12
18
24
30
36
42
48
54
60
Atrial specific rhythm control agents
Atrial specific action
Minimized risk of
ventricular proarrhythmias
Unspecific action
Risk of ventricular proarrhythmias
* New classes?
* Come away from
classes?
* Aventis, AZ,
Cardiome etc.
Ur FASS 2010 - Antiarytmika
Ur FASS 2010
Ur FASS 2010 – C01BB AA klass IB
Ur FASS 2010
Ur FASS 2010
Sotalol!!??
betablockerare och
QT-förlängning
Ur FASS 2010 – C01BG AA klass IV
Decreasing atrial fibrillation burden
is an important goal
As with heart failure or angina success in managing atrial fibrillation
Is defined as a decrease in
Frequency
of
episodes
Duration
of
episodes
Symptoms
during
episodes
Decreasing atrialfibillation burden offers potential to
Successfully treat atrial fibrillation by
* decreasing mortality
* decreasing hospitalizations
* increasing QoL
Prystowsky EN. J Cardiovasc Electrophysiol. 2006;17(suppl 2):S7-S10; Wolf PA et al. Arch Intern Med. 1998;158:229-234.
Long-term maintenance of SR
improves functional capacity - AFFIRM
0.50
Mean NYHA-FC score
0.45
0.40
0.35
0.30
0.25
(Lower NYHA-FC score = less
symptomatic)
0.20
0.15
Adjusted P<.0001
Current atrial fibrillation
0.10
No current atrial fibrillation
0.05
0
Initial
2
4
8
1
Months
Chung MK et al. J Am Coll Cardiol. 2005;46:1891-1899.
1⅓
1⅔
2
2⅓
2⅔
3
Years
3⅓
3⅔
4
4⅓
4⅔
5